{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:24:22Z","timestamp":1787325862725,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"47","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571603"],"award-info":[{"award-number":["32571603"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172084"],"award-info":[{"award-number":["82172084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["25ZR1402237"],"award-info":[{"award-number":["25ZR1402237"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Endogenous STING activation by mitochondrial DNA (mtDNA) offers a tumor\u2010context\u2010dependent strategy with potentially reduced off\u2010target toxicity, but is often limited by weak and transient mtDNA\u2010driven STING signaling that fails to sustain robust STING clustering. Here, we developed an on\u2010demand nanoparticle system that harnesses mitochondrial\u2013ER functional interplay by concurrently inducing mtDNA release and ER stress, thereby relieving the STIM1\u2010mediated brake on STING and enabling robust STING\u2013TBK1 assembly and downstream signaling. This strategy markedly increased the phosphorylation levels of STING, TBK1, and IRF3 by 11.50\u2010, 9.70\u2010, and 8.95\u2010fold, respectively, compared with PBS, outperforming the commercial STING agonist MSA\u20102 by more than 2\u2010fold. In addition, the nanoparticles enabled spatially controlled co\u2010delivery, allowing extracellular release of a PD\u20101\/PD\u2010L1 inhibitor and intracellular release of mtDNA\u2010releasing and ER stress\u2010inducing agents. Consequently, this on\u2010demand nanoparticle system potently enhanced both innate and adaptive antitumor immunity in vivo, significantly increasing CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration while reducing Tregs, ultimately suppressing tumor progression, metastasis, and recurrence in mouse models of breast and colon cancer. This strategy advances STING\u2010based immunotherapy by integrating spatially staged drug release with organelle\u2010level immune modulation.\n                  <\/jats:p>","DOI":"10.1002\/adma.74146","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T07:17:53Z","timestamp":1784272673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging Mitochondria\u2010Endoplasmic Reticulum Functional Interplay With an On\u2010Demand Nanoparticle to Boost mtDNA\u2010Based STING Immunotherapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Han","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Frontiers Science Center of Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory For Antibody\u2010Drug Conjugates 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